期刊
CELLULAR SIGNALLING
卷 25, 期 12, 页码 2652-2660出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2013.08.029
关键词
HGF/ETS-1 signaling; LINE-1 ORF-1p; Transcriptional activity; Protein-protein interaction; Triple negative breast cancer
类别
资金
- Key Scientific and Technological Research Foundation of the National Special Purpose Program [2012ZX1002D2DD, 2013ZX10005002]
- National Natural Science Foundation [81272330, 81202362]
Long interspersed nucleotide element (LINE)-1 ORF-1p is encoded by the human pro-oncogene LINE-1. It is involved in the development and progression of several human carcinomas, such as hepatocellular carcinoma and lung and breast cancers. The hepatocyte growth factor (HGF)/ETS-1 signaling pathway is involved in regulation of cancer cell proliferation, metastasis and invasion. The biological function of the interaction between LINE-1 ORF-1p and the HGF/ETS-1 signaling pathway in regulation of human breast cancer proliferation remains largely unknown. Here, we showed that LINE-1 ORF-1p enhanced ETS-1 transcriptional activity and increased expression of downstream genes of ETS-1. Interaction between ETS-1 and LINE-1 ORF-1p was identified by immunoprecipitation assays. LINE-1 ORF-1p modulated ETS-1 activity through cytoplasm/nucleus translocation and recruitment to the ETS-1 binding element in the MMP1 gene promoter. We also showed that LINE-1 ORF-1p promoted proliferation and anchorage-independent growth of MDA-MB-231 breast cancer cells. By investigating a novel role of the LINE-1 ORF-1 p in the HGF/ETS-1 signaling pathway and MDA-MB-231 cells, we demonstrated that LINE-1 ORF-1 p may be a novel ETS-1 coactivator and molecular target for therapy of human triple negative breast cancer. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.
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